Overexpression of heat shock protein 70 enhanced mesenchymal stem cell treatment efficacy in phosgene‐induced acute lung injury

Abstract

In our previous study, we have confirmed that in phosgene‐induced acute lung injury (ALI) rats, mesenchymal stem cells (MSCs) can treat the disease. Moreover, heat shock protein 70 (Hsp70) can be used as a protective protein, and Hsp70 upregulated drastically when exposed to stressful conditions. We aimed to assess that MSCs overexpressed Hsp70 could enhance the capacity of MSCs and have a good therapeutic effect on phosgene‐induced ALI. We transduced MSCs with Hsp70 and then we tested the function of the transduced MSCs. Sprague Dawley rats inhaled phosgene in a closed container for 5 minutes. The transduced MSCs and MSCs were administered via the trachea immediately. Rats in each group were killed at 6, 24, and 48 hours after exposure. Compared to MSCs, MSCs overexpressed Hsp70 enhanced MSCs viability, antiapoptotic ability, and migration ability, and these effects disappeared when using the phosphatidylinositol 3‑kinase/protein kinase B (PI3K/AKT) pathway inhibitor. Furthermore, the results of pathological alterations improved. The lung wet‐to‐dry ratio declined. The lung injury index total protein content and total cells in bronchoalveolar lavage fluid (BALF) also declined. The level of tumor necrosis factor α declined and the level of interleukin‐10 improved in BALF and serum. MSCs overexpressed Hsp70 can enhance the capacity and efficacy of MSCs in the treatment of phosgene‐induced ALI and may be mediated through the PI3k/AKT signaling pathway. This article introduces a new approach to stem cell therapy for improving the efficacy of phosgene‐induced ALI.

Lung‐derived exosomes regulate the function of mesenchymal stem cells and alleviate phosgene‐induced lung injury via miR‐34c‐3p

“…[26] Furthermore, MSCs pretreated via different methods could have a better therapeutic effect on phosgene-induced ALI than nonpretreated MSCs. [27,28] The exosome is an essential microenvironment that affects cell function. [29] For instance, exosomes released by breast cancer cells could transform MSCs into tumor-forming cells.…”

“…[ 26 ] Furthermore, MSCs pretreated via different methods could have a better therapeutic effect on phosgene‐induced ALI than nonpretreated MSCs. [ 27,28 ]…”

Phosgene-Induced acute lung injury: Approaches for mechanism-based treatment strategies

“…Further studies have confirmed the related mechanisms of action from various aspects, including regulation of the proliferation and differentiation of lung epithelial cells and endogenous lung stem cells ( 56 ) and repair via the proliferation of endogenous lung stem cells ( 94 ). Although most studies focusing on experimental models have demonstrated their validity, MSCs provide strong prospects for treating P-ALI ( 6 , 52 , 53 , 94 – 98 ) ( Table 2 ). MSC-based therapy has been widely used in the clinical treatment stage of ARDS and has also achieved very good effects, and it is expected to be studied in the P-ALI clinic in the near future.…”

Mechanism of Phosgene-Induced Acute Lung Injury and Treatment Strategy

“…Modifying MSCs to enhance their homing and migration abilities has achieved initial success in a P-ALI animal model. Jin et al used MSCs overexpressing heat shock protein 70 (Hsp70) to treat P-ALI and surprisingly found that Hsp70 activated the PI3K/AKT pathway to promote MSC survival and migration [96]. In addition, by upregulating the level of the SDF1-specific receptor CXCR7, the ability of MSCs to directionally migrate and differentiate into ATII could be enhanced [97,98].…”